179 results about "Eosinophil" patented technology

Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: wherein j is 0 or 1, k is 0 or 1, m is 0, 1, or 2; n is 1 or 2; A is selected from the partial Formulas: where q is 1, 2, or 3, W3 is -O-; -N(R9)-; or -OC(=O)-; R7 is selected from -H; -(C1-C6) alkyl, -(C2-C6) alkenyl, or -(C2-C6) alkynyl substituted by 0 to 3 substituents R10; -(CH2)u-(C3-C7) cycloalkyl where u is 0, 1 or 2, substituted by 0 to 3 R10; and phenyl or benzyl substituted by 0 to 3 R14; R8 is tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-on-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-on-3-yl; 1,2,4-oxadiazol-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinyl; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onyl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; indolyl; indolinyl; isoindolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazolo[3,4-d]pyrimidinyl; pyrimido[4,5-d]pyrimidinyl; imidazo[1,2-a]pyridinyl; pyridopyridinyl; pteridinyl; or 1H-purinyl; or A is selected from phosphorous and sulfur acid groups; W is -O-; -S(=O)t-, where t is 0, 1, or 2; or -N(R3)-; Y is =C(R1a)-, or -[N<custom-character file="US20020111495A1-20020815-P00900.TIF" wi="20" he="20" id="custom-character-00001" / >(O)k] where k is 0 or 1; R4, R5 and R6 are (1) -H; provided that R5 and R6 are not both -H at the same time, -F; -Cl; -(C2-C4) alkynyl; -R16; -OR16; -S(=O)pR16; -C(=O)R16, -C(=O)OR16, -C(=O)OR<highlight><sup

The present invention relates to a method of reducing the numbers of eosinophils in a human subject comprising administration to a subject an IL-5R binding molecule that comprises (a) a region that specifically binds to the IL-5R and (b) an immunoglobulin Fc region. In a specific embodiment, a method of the invention reduces the number of eosinophils in blood, bone marrow, gastrointestinal tract (e g, esophagus, stomach, small intestine and colon), or lung.

Provided herein are methods for treating gastrointestinal inflammation, for example, esophageal inflammation, or reduction of eosinophilic infiltration of the esophagus and / or reducing local and systemic exposure and / or side effects resulting therefrom. Provided herein are methods for diagnosing gastrointestinal inflammation, for example, esophageal inflammation, or reduction of eosinophilic infiltration of the esophagus. Also provided herein are methods for inducing remission of eosinophilic infiltration of the esophagus

Conjugates containing as a ligand a chemokine receptor targeting agents, such as chemokines, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophiles, macrophages, and eosinophils. The conjugates provided herein are used to lessen or inhibit these processes to prevent or at least lessen the resulting secondary effects. In particular, the conjugates are used to target toxins to receptors on secondary tissue damage-promoting cells. The ligand moiety can be selected to deliver the cell toxin to such secondary tissue damage-promoting cells as mononuclear phagocytes, leukocytes, natural killer cells, dendritic cells, and T and B lymphocytes, thereby suppressing the proliferation, migration, or physiological activity of such cells. Among preferred conjugates are fusion proteins having a chemokine, or a biologically active fragment thereof, as the ligand moiety linked to a cell toxin via a peptide linker of from 2 to about 60 amino acid residues.

The invention relates to the genetic engineering field, especially to a strain Bispora sp.MEY-1 which produces an acidophilic beta-mannanase and the acidophilic beta-mannanase MAN5A got from the strain having an amino acid sequence shown as SEQ ID NO.1 or 2, a gene man5A for coding said beta-mannanase having a nucleotide sequence shown as SEQ ID NO.1 or 2, and a recombinant vector containing said gene and applications. The beta-mannanase of the invention has the following advantages: the optimum pH 1.0-1.5, the optimum temperature 65 DEG C, good pH stability and thermostability, high specific activity, good protease resistance and easy for industrial fermentation production. The product of the invention can be widely used for the animal feeding-stuffs, the food, the medicament, the brewing and the energy industry as a novel enzyme preparation.

An exemplary embodiment of apparatus and method according to the present disclosure can be provided. For example, using at least one first arrangement, it is possible to direct at least one first electro-magnetic radiation to at least one portion of tissue within a body. Using at least one second arrangement, it is possible to receive at least one second electro-magnetic radiation provided from the portion, which is based on the first electro-magnetic radiation. Further, using at least one third arrangement, it is possible to differentiate at least one particular cell which is eosinophil, mast cell, basophil, monocyte and / or nutrophil from other cells in the portion based on the second electro-magnetic radiation.

Genes whose expression differ between that in eosinophils collected from atopic dermatitis patients of the exabartation stage and those of the remission stage were searched via a differential display method. As a result, NOR-1 (MINOR) gene was successfully identified whose expression significantly increased in eosinophils of patients in the remission stage, a stage associated with a decrease of eosinophils. The present inventors discovered that the gene can be successfully employed in testing for allergic diseases and screening for candidate compounds for therapeutic agents.

The present invention relates to a method of reducing the numbers of eosinophils in a human subject comprising administration to a subject an IL-5R binding molecule that comprises (a) a region that specifically binds to the IL-5R and (b) an immunoglobulin Fc region. In a specific embodiment, a method of the invention reduces the number of eosinophils in blood, bone marrow, gastrointestinal tract (e.g. esophagus, stomach, small intestine and colon), or lung.

This invention relates to a method to protect a mammal from a disease associated with an inflammatory response, and in particular, from an inflammatory disease characterized by eosinophilia, airway hyperresponsiveness and / or a Th2-type immune response. The method includes administration of a heat shock protein to a mammal having such a disease. Formulations useful in the present method are also disclosed.

The present invention provides a human eosinophil-derived basic protein (EBPH) and polynucleotides which identify and encode EBPH. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding EBPH and a method for producing EBPH. The invention also provides for use of EBPH and agonists, antibodies or antagonists specifically binding EBPH, in the prevention and treatment of diseases associated with expression of EBPH. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding EBPH for the treatment of diseases associated with the expression of EBPH. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding EBPH.

The present invention relates to a novel compound or a salt thereof, which is useful as a CRTH2 antagonist, especially as a medicament for disorder that participates eosinophil, for example, allergic disorder such as asthma, allergic rhinitis, allergic dermatitis, conjunctival inflammation, hives, eosinophilic bronchitis, food allergy, inflammation of the nasal sinuses, multiple sclerosis, angiitis, or chronic obstructive pulmonary disease (COPD) and the like.

CD48, a surface-marker molecule present in eosinophils, is disclosed herein as a key molecule in allergic conditions, particularly in allergic airway inflammations like asthma, allergy and nasal polyposis. CD48 is thus presented as a target molecule in the treatment of said conditions. In addition, diagnostic methods, and a kit for the diagnosis of allergic inflammatory conditions are described, based on the detection of CD48 expression.

The invention relates to model systems for allergic conditions, and in particular to in vivo model systems in a large animal. The model systems of the invention are especially useful for providing large numbers of activated or non-activated eosinophils, for the discovery and evaluation of novel anti-inflammatory drug targets and for providing a model for the in vivo study of asthma and the effects of allergy treatments. In a preferred embodiment the animal is a sheep. In one embodiment, repeated infusion of house dust mite allergen (HDM) into the mammary gland is used to induce a specific allergic response, which is characterised by the recruitment of inflammatory cells, particularly eosinophils, into the mammary lumen; these cells can be harvested from peripheral blood and mammary lavage (MAL). In a second embodiment, the mammal is immunised with soluble antigen, for example by repeated subcutaneous immunisation, and then subjected to a single challenge with the same antigen administered directly to the lung.

The invention provides humanized anti-Siglec-8 antibodies and their use in treating and preventing eosinophil-mediated disorders and / or mast cell-mediated disorders, as well as compositions and kits comprising the humanized anti-Siglec-8 antibodies.

The present invention provides peptide-based peroxidase inhibitors having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2 or a retro or retro-inverso analog thereof. The result of such a combination is a highly effective inhibitor of peroxidase activity that has potent anti-inflammatory properties in widely diverse models of vascular disease and injury. Exemplary tripeptides effectively inhibit peroxidase mediated LDL oxidation, increase vasodilation in SCD mice, inhibit eosinophil infiltration and collagen deposition in asthma mice, inhibit acute lung injury, and decrease ischemic injury of the heart.

A method of establishing a differential white blood cell count includes directing at least one stream of deionized water into a microfluidic device containing a sample of whole blood or a cell-rich fraction to generate a lysate stream of intact white blood cells; directing at least one stream of deionized water into the lysate stream to form a virtual non-conductive aperture in a channel of the device; and performing impedance cytometry of the lysate stream via coplanar electrodes to detect the presence of intact white blood cells. A microfluidic device includes a blood separation section. An analyte sensor detects electrical changes in a cell-free fraction. Lysate from a cell-rich fraction is analyzed to detect circulating tumor cells or white blood cells including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. A method of fabricating and a standalone cell-rich microfluidic device are disclosed for differential white blood cell counts.

The present invention relates to a method of reducing the numbers of eosinophils in a human subject comprising administration to a subject an IL-5R binding molecule that comprises (a) a region that specifically binds to the IL-5R and (b) an immunoglobulin Fc region. In a specific embodiment, a method of the invention reduces the number of eosinophils in blood, bone marrow, gastrointestinal tract (e.g. esophagus, stomach, small intestine and colon), or lung.

A method for reducing cytotoxicity of eosinophil derived toxins comprising administering to a subject an effective amount of heparin, heparan sulfate, a potent heparanase inhibitor or a polypeptide which has sequence as follows: BZBXBX, XBBBXXBX, XBBXBX, BBXXBBBXXBB, BXBBXB, XBBBXXBBBXXBBX, or TXXBXXTBXXXTBB, wherein X represents any amino acid, Z represents an aromatic amino acid, and B represents a basic amino acid and T represents a turn.

A method of treating inflammatory bowel disease (IBD) comprises providing an intestinal biopsy sample obtained from inflamed tissue of a patient; mechanically treating the sample to obtain a cell suspension; identifying cell surface markers of activated leukocytes selected from T lymphocytes, neutrophil granulocytes, and eosinophil granulocytes in the suspension; raising antibodies against one of more of the activated cells and immobilizing them on a support; providing a column loaded with the support; diverting a portion of the patient's peripheral blood to make it pass through the column before re-infusing it to the patient to make the activated leukocytes couple with antibodies on the support, thereby eliminating them from the blood stream. Also disclosed are corresponding columns and supports, and their use in the method.

The invention provides humanized anti-Siglec-8 antibodies and their use in treating and preventing eosinophil-mediated disorders and / or mast cell-mediated disorders, as well as compositions and kits comprising the humanized anti-Siglec-8 antibodies.

Disclosed are bi-specific complexes aimed at inhibiting mast cells, eosinophils and / or basophils, and thus, at inhibiting allergy-type reactions. In particular, said complexes are best exemplified by bi-specific antibodies, which bind to two targets present in the same cell. One target is the inhibitory receptor IRp60. The second target is a cell-specific activator, e.g. IgE, cKIT, FcεRI, IL5R or CCR3. Binding of the bi-specific antibody to its targets results in the induction of an inhibitory pathway, through the inhibition of the signaling from the activator. Compositions and uses of the bi-specific complexes are also described.

The present invention relates to a pyrimidine derivative of the formula (I) and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The pyrimidine derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.

The invention provides methods and compositions useful for inducing or enhancing an immune response in a human or non-human animal. In an embodiment, the method involves administering an antigen-presenting cell chemotaxin, such as a chemokine polypeptide or variant thereof, optionally with administration of an antigen. In some embodiments, the chemokine or variant is chemotactic for dendritic cells and / or macrophages, but not chemotactic for one or more of neutrophils, T-lymphocytes, monocytes, or eosinophils. In an embodiment, the chemokine or variant is a chemotaxin for immature but not mature dendritic cells.

A detection method and an apparatus of activated neutrophils are provided, to provide a detection method of activated neutrophils enabling the classification of normal leukocytes and the detection of activated neutrophils, a measurement sample in which erythrocytes in a biotic sample are hemolyzed and nucleic acid of leukocytes is stained by a nucleic acid staining fluorochrome is prepared, the sample is irradiated with light, and leukocytes in the biotic sample are classified into at least a cluster containing neutrophils and a cluster containing eosinophils based on scattered light intensity and fluorescence intensity obtained by measuring the scattered light intensity and fluorescence intensity generated from particles in the sample to detect particles present between the cluster containing neutrophils and the cluster containing eosinophils as activated neutrophils.

Embodiments of the invention are directed to methods of diagnosing eosinophilic gastritis (EG), or remission therefrom in a subject, wherein the methods include applying a sample from the subject to a diagnostic panel that contains selected markers for EG, analyzing the results thereof, and making a determination as to the EG status of the subject. Embodiments of the invention are also directed to methods of monitoring the pathological development or medical prognosis of EG in a subject. Embodiments of the invention are also directed to use of CDH26 as a marker for EG, eosinophilic esophagitis, or allergic inflammatory conditions. Embodiments of the invention also relate to the use of anti-CDH26-based therapeutics to treat allergic inflammatory conditions.

A probiotic lactobacillus was discovered from lactobacilli of the Lactobacillus genus independently isolated from human adult feces. The probiotic lactobacillus was selected from other bacterial strains for: (1) being highly resistant to gastric acid / bile acid; (2) having a high promoting activity on IL-12 production from mouse derived spleen cells and a high Th1 / Th2 balance-improving effect; (3) having a high ability to inhibit the production of antigen-specific IgE induced by intraperitoneally administering ovalbumin to BALB / c mice; (4) having a high ability to inhibit the production of antigen-specific IgE induced by orally administering a food antigen to C57BL / 6N mice; (5) having a high Natural Killer cell-activating ability; (6) having a high IL-12 production-promoting activity on spleen cells and mesenteric lymph node cells derived from mice immunized with ovalbumin and a high Th1 / Th2 balance-improving effect; and (7) having a high ability to suppress eosinophilia induced by a cedar pollen-extracted antigen. This discovery led to the completion of the present invention.